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Background: Sacituzumab govitecan has been recently approved by the USFDA and EMA for the treatment of patients with metastatic triple-negative breast cancer (mTNBC). We report real-world safety and effectiveness in patients with mTNBC receiving sacituzumab govitecan treatment at a breast cancer centre in Germany. Methods: Data from patients who had received sacituzumab govitecan as treatment for mTNBC, in both de novo and relapsed disease, at the Kliniken Essen-Mitte, Essen, Germany, were collected through institutional records. Data were analysed for safety parameters and survival outcomes and reported using descriptive statistics. Results: Patients (N = 43) received a median (range) of 5 (1–28) cycles of sacituzumab govitecan and were followed up for a median of 12.9 months. The most reported adverse events (AEs) of any grade were alopecia (n = 39; 90.7%), diarrhoea (n = 16; 37.2%), fatigue (n = 15, 34.9%), anaemia (n = 15, 34.9%) and neutropenia (n = 14, 32.6%). AEs ⩾ Grade 3 with the highest incidence were neutropenia (n = 12; 27.9%) and diarrhoea (n = 8; 18.6%). In eight (18.6%) patients, dose of sacituzumab govitecan dose was reduced due to patients’ clinical condition prior to commencing treatment; in further 17 (39.5%) patients, sacituzumab govitecan dose had to be reduced or treatment interrupted on account of AEs associated with the drug after treatment had commenced. Median progression-free survival and median overall survival were calculated to be 5.0and 13.1 months, respectively. Conclusion: The real-world safety and effectiveness profile of sacituzumab govitecan in patients with mTNBC are in line with clinical trial data. Further studies are required to guide optimal use of sacituzumab govitecan against mTNBC, especially in context of management of accompanying AEs.

ObjectiveAdult granulosa cell tumors represent less than 5% of all ovarian malignancies. The aim of this study was to analyze the clinicopathological parameters and their impact on progression-free and overall survival.MethodsPatients with primary adult granulosa cell tumors treated in three international referral centers between July 1999 and December 2018 were included. The following data were anonymously exported from the prospective database: age at diagnosis, International Federation of Gynecology and Obstetrics (FIGO) stage, adjuvant therapy, surgical procedures, progression-free survival, and overall survival. Descriptive statistical analysis regarding tumor and treatment characteristics was performed. Survival analyses included Kaplan–Meier functions and Cox proportional hazard ratios (HR).ResultsA total of 168 patients with primary adult granulosa cell tumors were included. Median age was 50 years (range 13–82). With regard to stage distribution, 54.2% (n=91) of patients were FIGO stage IA, 1.2% (n=2) were stage IB, 26.8% (n=45) were stage IC, and 17.9% (n=30) were FIGO stage II–IV. 66.7% (n=112) of patients underwent surgical restaging, of whom 17.9% (n=20) were moved to a higher stage. In addition, 36 (21.4%) patients underwent fertility-sparing surgery. After a median follow-up of 61 months (range 0–209), 10.7% of patients (n=18) had recurrent disease and 4.8% (n=8) died of disease. Five-year progression-free survival was 86.1% and estimated overall survival was 95.7%. Five-year progression-free survival was worse for patients with advanced stages (FIGO stage IA/B vs IC: HR 5.09 (95% CI 1.53 to 16.9); FIGO stage IA/B vs II–IV: HR 5.62 (95% CI 1.58 to 19.9)). Nineteen patients receiving adjuvant chemotherapy had lower estimated 5-year progression-free survival compared with patients not receiving chemotherapy (49.7% vs 91.1%, p<0.001; HR 9.15 (95% CI 3.62 to 23.1)).ConclusionThe prognosis of patients with primary adult granulosa cell tumors is mainly determined by FIGO stage. The outcome of patients with FIGO stage IC is comparable to those with advanced stages. Fertility-sparing surgery seems to be a safe procedure in stage IA. Our data do not support the use of adjuvant chemotherapy in early and advanced stages of adult granulosa cell tumors.

The utility of multigene expression assays in advanced (≥ 4 positive lymph nodes) early breast cancer (EBC) is limited. We conducted exploratory transcriptomic analysis of 758 genes (Breast Cancer 360 panel, nCounter® platform; NanoString) in primary tumor samples collected during a phase 3 trial comparing adjuvant taxane‐containing dose‐dense chemotherapy (ddCTX) versus standard‐dosed chemotherapy (stCTX) in resected EBC with ≥ 4 positive lymph nodes. Prognostic and predictive associations with disease‐free survival (DFS) and overall survival (OS) were evaluated by Cox regression with false discovery rate (FDR) adjustment. Data were available from tumor samples of 141/226 patients (median follow‐up: 14 years). Several genes/signatures, including immune markers, showed prognostic relevance in unadjusted analyses. Of these, two remained significant after multiplicity adjustment: a positive effect on DFS of programmed cell death 1 ligand‐2 (PD‐L2) in the ddCTX arm (univariate HR: 0.53, FDR‐adjusted P = 0.036) and a negative effect on OS of HER2‐enriched (HER2‐E) signature in the stCTX arm (univariate HR: 5.40, FDR‐adjusted P = 0.036). Predictive analyses showed greater DFS benefit of ddCTX in tumors with high antigen processing machinery (APM) expression (multivariate interaction P = 0.024). Multigene expression assays have a prognostic and predictive potential in advanced EBC, and further investigation is warranted in order to identify candidates for de‐escalated treatment. In addition, intrinsic subtype and immune gene expression have predictive potential. Early breast cancer patients with advanced nodal involvement have a varied course of disease, thereby constituting a clinically high‐risk subgroup. High‐throughput transcriptomic analyses provide a snapshot of gene expression patterns in tumors. This strategy has the potential to identify prognostic and predictive genes and gene signatures, which could further guide in the selection of appropriate treatment regimens.

ObjectiveThis international study aimed to investigate the impact of substage, histological type and other prognostic factors on long-term survival for stage I ovarian carcinoma.MethodsOur study was a retrospective multicenter cohort study that included patients with the International Federation of Gynecology and Obstetrics (FIGO) stage I (IA-IC3) ovarian carcinoma treated at four European referral centers in Germany and Italy. Using Kaplan-Meier survival curves we compared overall and disease-free survival between the different stage I groups.ResultsA total of 1115 patients were included. Of these, 48.4% (n=540) were in stage IA, 6.6% (n=73) stage IB, and 45% (n=502) stage IC, of the latter substage IC1, 54% (n=271), substage IC2, 31.5% (n=158), and substage IC3, 14.5% (n=73). Five-year overall and disease-free survival rates for the entire cohort were 94% and 86%, respectively, with no difference between stage IA and IB. However, there was a significantly better overall and disease-free survival for stage IA as compared with stage IC (p=0.007 and p<0.001, respectively). Multivariate analysis revealed incomplete/fertility-sparing staging (HR 1.95; 95% CI 1.27 to 2.99, and HR 3.54; 95% CI 1.83 to 6.86, respectively), and stage IC (HR 2.47; 95% CI 1.63 to 3.75) as independent risk factors for inferior disease-free survival, while low-grade endometrioid (HR 0.42; 95% CI 0.25 to 0.72) and low-grade mucinous (HR 0.17; 95% CI 0.06 to 0.44) histology had superior disease-free survival. Considering overall survival, stage IC (HR 2.41; 95% CI 1.45 to 4.01) and older age (HR 2.41; 95% CI 1.46 to 3.95) were independent risk factors.ConclusionAlthough stage I ovarian carcinoma exhibited excellent outcomes, the prognosis of patients with stage IA differs significantly compared with stage IC. Sub-optimal staging as an indicator for quality of care, and tumor biology defined by histology (low-grade endometrioid/mucinous) independently impact disease-free survival.

Background This study was designed to evaluate the prevalence, morbidity, and prognostic impact of port-site metastasis (PSM) in patients with epithelial ovarian cancer (EOC) undergoing laparoscopy before subsequent primary debulking surgery (PDS). Methods All consecutive patients treated between 2000 and 2014, who had a laparoscopy followed by PDS, were extracted from our prospectively maintained database. All patients with histological examination of port-sites were included in this unicentric exploratory analysis. Results A total of 250 (25.5 %) of 982 patients with EOC underwent laparoscopy before PDS. Port-site resection was performed in those 214 (85.6 %) patients in whom a complete or almost complete resection with residuals ≤1 cm was achieved. Median interval between laparoscopy and PDS was 25 days. PSM was detected in 100 of 214 patients (46.7 %). Risk factors for PSM were higher tumor stage (odds ratio [OR] 13.5, 95 % confidence interval [CI] 2.9–62.0, p  = 0.04), positive lymph node status (OR 3.0, 95 % CI 1.3–6.7, p  = 0.009), and ascites >500 mL (OR 3.9, 95 % CI 1.5–10.0, p  = 0.005). Wound healing disorders and postoperative morbidity were significantly higher in patients with PSM (Clavien–Dindo Classification grade 3–5: 41.0 vs. 14.9 %, p  < 0.001). However, multivariate Cox-regression models did not identify PSM as independent prognostic factor. Conclusions The prevalence of PSM after laparoscopy in EOC patients is considerably high. PSM had no impact on survival; however, PSM were associated with more postoperative complications and a higher surgical treatment burden. This should be balanced with the expected benefit when laparoscopy is considered for the management of EOC.

We present a versatile method for the preparation of mesoporous tin-doped indium oxide (ITO) thin films via dip-coating. Two poly(isobutylene)-b-poly(ethyleneoxide) (PIB-PEO) copolymers of significantly different molecular weight (denoted as PIB-PEO 3000 and PIB-PEO 20000) are used as templates and are compared with non-templated films to clarify the effect of the template size on the crystallization and, thus, on the electrochemical properties of mesoporous ITO films. Transparent, mesoporous, conductive coatings are obtained after annealing at 500 °C; these coatings have a specific resistance of 0.5 Ω cm at a thickness of about 100 nm. Electrical conductivity is improved by one order of magnitude by annealing under a reducing atmosphere. The two types of PIB-PEO block copolymers create mesopores with in-plane diameters of 20-25 and 35-45 nm, the latter also possessing correspondingly thicker pore walls. Impedance measurements reveal that the conductivity is significantly higher for films prepared with the template generating larger mesopores. Because of the same size of the primary nanoparticles, the enhanced conductivity is attributed to a higher conduction path cross section. Prussian blue was deposited electrochemically within the films, thus confirming the accessibility of their pores and their functionality as electrode material.

Background: Chromosomal instability, a hallmark of cancer, results in changes in the copy number state. These deviant copy number states can be detected in the cell-free DNA (cfDNA) and provide a quantitative measure of the ctDNA levels by converting cfDNA next-generation sequencing results into a genome-wide copy number instability score (CNI-Score). Our aim was to determine the role of the CNI-Score in detecting epithelial ovarian cancer (EOC) and its role as a marker to monitor the response to treatment. Methods: Blood samples were prospectively collected from 109 patients with high-grade EOC. cfDNA was extracted and analyzed using a clinical-grade assay designed to calculate a genome-wide CNI-Score from low-coverage sequencing data. Stored data from 241 apparently healthy controls were used as a reference set. Results: Comparison of the CNI-Scores of primary EOC patients versus controls yielded sensitivities of 91% at a specificity of 95% to detect OC, respectively. Significantly elevated CNI-Scores were detected in primary (median: 87, IQR: 351) and recurrent (median: 346, IQR: 1891) blood samples. Substantially reduced CNI-Scores were detected after primary debulking surgery. Using a cut-off of 24, a diagnostic sensitivity of 87% for primary and recurrent EOC was determined at a specificity of 95%. CNI-Scores above this threshold were detected in 21/23 primary tumor (91%), 36/42 of platinum-eligible recurrent (85.7%), and 19/22 of non-platinum-eligible recurrent (86.3%) samples, respectively. Conclusion: ctDNA-quantification based on genomic instability determined by the CNI-Score was a biomarker with high diagnostic accuracy in high-grade EOC. The applied assay might be a promising tool for diagnostics and therapy monitoring, as it requires no a priori information about the tumor.

Purpose The chemotherapy response score (CRS) is a histopathological tool to evaluate response to neoadjuvant chemotherapy (NACT) in high-grade serous ovarian cancer (OC). We critically evaluated the clinical value of CRS and compared its predictive power to standard serological (CA125) and radiological response. Methods A retrospective analysis of 277 OC patients, who received primary chemotherapy, was performed. CRS, serological, and radiological findings were correlated with progression-free (PFS) and overall survival (OS). Results CRS could be determined in 172 of 277 patients (62.1%). In patients with CRS3, a longer median PFS and OS was observed compared with CRS1/2 patients (31.2 vs. 18.9, P  < 0.001; 55.0 vs. 36.1 months, P  = 0.050). CA125 and radiological response evaluation were also predictive for PFS and OS. Patients with serological and radiological complete response showed longer PFS (23.0 vs. 14.4, P  = 0.011; 21.4 vs. 9.6 months, P  < 0.001) and OS (49.5 vs. 29.0, P  = 0.003; 45.0 vs. 12.9 months, P  < 0.001). Patients with pathological complete response (pCR) had the best median PFS (52.8 months), even compared with non-pCR CRS3 (27.8 months). In the total study cohort, serological, and radiological complete response was better at predicting PFS (hazard ratio 2.23 and 2.77). Conclusion In this study, evaluation of response to chemotherapy by CRS was not superior to conventional methods (CA125 or radiology). Independent of the evaluation method, response to NACT was predictive of PFS and OS. We observed no added value for CRS as a prognostic marker. The clinical relevance of CRS should be discussed, as no therapeutic consequences result from CRS evaluation.

IntroductionHereditary factor (F) XIII-deficiency is a known risk factor for postoperative complications, but data of acquired FXIII-deficiency in malignancies are limited. Therefore, we evaluated the role of acquired FXIII-deficiency in surgery for advanced epithelial ovarian cancer (EOC).Materials and methodsWe performed a retrospective analysis of patients with known serum FXIII status and treatment between 2011 and 2018 at our center. We defined cohorts according to FXIII with values > 75% as normal (group A), 55–75% as reduced (group B) and < 55% as low (group C). Complications were classified according to the Clavien–Dindo Classification, class III–V complications were defined as severe.Results347 patients with EOC were identified. 180 patients (51.2%) were in group A, 82 patients (23.6%) in group B, and 85 patients (24.4%) in group C. Lower levels of FXIII were associated with higher amount of ascites, FIGO IV, high grade serous histology, low albumin, and higher CA-125 levels. Regarding intraoperative variables, low FXIII was associated with longer duration of surgery, higher blood loss, higher surgical complexity score/number of bowel anastomosis and a higher probability for macroscopic residual disease. The risk of severe complications in group A was 12.2%, 24.4% in group B, and 31.8% in group C. In a multivariate model, low FXIII (OR 2.8), > 1 bowel anastomosis (OR 2.7), age-adjusted Charlson comorbidity index ≥ 4 (OR 3.6) and a longer duration of surgery (> 285 min.) were significant predictive factors for severe complications.ConclusionFXIII is associated with tumor and treatment burden. A low level of FXIII is associated with postoperative complications. The knowledge about the presurgical serum FXIII-level might be helpful to plan the treatment strategy.

OBJECTIVESThis study aimed to compare the prognosis of patients with synchronous endometrial and ovarian cancer (SEOC) to matched controls with either endometrial cancer (EC) or ovarian cancer (OC). METHODSA retrospective case-control study including all patients with SEOC who had been treated at 5 European tertiary gynecologic oncology centers between 1996 and 2011 and patients with either EC or OC matched for age, International Federation of Gynecology and Obstetrics (FIGO) stage, histology, year of diagnosis, and Eastern Cooperative Oncology Group performance score. RESULTSThe study cohort comprised 77, 132, and 126 patients with SEOC, EC, and OC, respectively. The patient characteristics confirmed an equal distribution of matching factors, and the median follow-up did not differ (P = 0.44). 48.1% of the patients with SEOC showed early FIGO stage I for both EC and OC. The 5-year PFS rates differed between SEOC and EC (76.3% vs 86.3%; P = 0.047) but not the 5-year overall survival rates (71.6% vs 79.8%; P = 0.12) and did not differ between SEOC and OC (76.3% vs 63.8%; P = 0.19 and 71.6% vs 69.3%; P = 0.61, respectively). After the adjustment for the FIGO stage of the 2 components of SEOC, neither PFS nor overall survival rates were different. CONCLUSIONSPrognosis of patients with SEOC tended to be the same in comparison with matched controls with either one EC or OC. Therefore, it could be considered that patients with SEOC may be eligible for clinical trials of the advanced tumor component if no additional therapy is indicated for the other component.